Bingham P M, Scott M O, Wang S, McPhaul M J, Wilson E M, Garbern J Y, Merry D E, Fischbeck K H
Division of Neurology, Children's Hospital of Philadelphia, Pennsylvania, USA.
Nat Genet. 1995 Feb;9(2):191-6. doi: 10.1038/ng0295-191.
The expansion of trinucleotide repeat sequences underlies a number of hereditary neurological disorders. To study the stability of a trinucleotide repeat and to develop an animal model of one of these disorders, spinal and bulbar muscular atrophy (SBMA), we have generated transgenic mice carrying either the normal or expanded repeat human androgen receptor (AR) gene. Unlike the disease allele in humans, the AR cDNA containing the expanded repeat in transgenic mice showed no change in repeat length with transmission. Expression of the SBMA AR was found in transgenic mice, but at a lower level than normal endogenous expression. The lack of a physiological pattern of expression may explain why no phenotypic effects of the transgene were observed.
三核苷酸重复序列的扩增是多种遗传性神经疾病的基础。为了研究三核苷酸重复序列的稳定性，并开发其中一种疾病——脊髓延髓肌萎缩症（SBMA）的动物模型，我们构建了携带正常或扩增重复序列的人类雄激素受体（AR）基因的转基因小鼠。与人类的疾病等位基因不同，转基因小鼠中含有扩增重复序列的AR cDNA在传递过程中重复长度没有变化。在转基因小鼠中发现了SBMA AR的表达，但水平低于正常内源性表达。缺乏生理性表达模式可能解释了为何未观察到转基因的表型效应。
